Abstract

Habitual physical activity and regular exercise training improve cardiovascular health and longevity. A physically active lifestyle is, therefore, a key aspect of primary and secondary prevention strategies. An appropriate volume and intensity are essential to maximally benefit from exercise interventions. This document summarizes available evidence on the relationship between the exercise volume and risk reductions in cardiovascular morbidity and mortality. Furthermore, the risks and benefits of moderate- versus high-intensity exercise interventions are compared. Findings are presented for the general population and cardiac patients eligible for cardiac rehabilitation. Finally, the controversy of excessive volumes of exercise in the athletic population is discussed.

Habitual physical activity and exercise training reduce cardiovascular disease (CVD) morbidity and mortality (1,2). The 2008 Physical Activity Guidelines Advisory Committee Report recommended 150 min/week of moderate-intensity or 75 min/week of vigorous-intensity aerobic exercise for all U.S. adults (Table 1) (3), because this exercise volume provides significant health improvements for most people much of the time. However, only one-half of Americans meet these guidelines (4). In contrast, participation in endurance exercise races has grown in popularity among the most active individuals, as demonstrated by the marked increase in the number of participants in marathons, triathlons, and cycling races over the past 3 decades (5,6). These individuals typically engage in aerobic exercise volumes and intensities well above the 2008 guideline recommendations. Several recent reports surprisingly suggest that high volumes of aerobic exercise may be as bad for CVD outcomes as physical inactivity (7–10). The public media has embraced the idea that exercise may harm the heart and disseminated this message, thereby diverting attention away from the benefits of exercise as a potent intervention for the primary and secondary prevention of heart disease (11). This document will review the published data on the volume and intensity of aerobic exercise required for favorable cardiovascular health and will also address the question as to whether or not there is a volume that increases CVD risk.

Exercise in Primary Prevention

General benefits of exercise

The health benefits of exercise have been recognized since the epidemiological studies of Morris et al. (13), who in the 1950s reported lower rates of coronary heart disease among the conductors of London’s double-decker buses compared with the drivers. Morris et al. (13) also reported a lower incidence of coronary heart disease among English postmen compared with telephone operators working at the same company. These data were the first to illustrate an association between habitual physical activity and cardiovascular health. Many subsequent epidemiological studies confirmed this inverse relationship between physical activity and CVD (14–16), but none have proven causation because all such studies are observational. To date, there are no randomized clinical trials directly testing whether physical activity prevents CVD. Such a study would require an enormous sample size and study duration because of subject crossover among those volunteering for an “exercise study” and because the progressively lower rates of primary CVD in the general population would reduce CVD endpoints. Powell et al. (17) evaluated the possibly causative relationship between physical activity and cardiovascular disease using the same criteria used to document a causative relationship between cigarette smoking and health (18), a relationship also lacking a randomized, controlled clinical trial. They demonstrated that the relationship between physical activity and CVD was strong, was consistent among studies, had a graded risk reduction with increasing exercise volumes, and was coherent with clinical studies showing a putatively beneficial effect of exercise on CVD risk factors (17). They concluded that increasing physical activity was causally related to lower rates of CVD despite the absence of the classical clinical trial.

Dose-response relationship between physical activity and mortality

The association between exercise or physical activity and CVD outcome is most frequently described as a curvilinear relationship (Figure 1) (26). This indicates that a change from an inactive to a mild or moderately active lifestyle yields a relatively large risk reduction, whereas further increasing exercise volumes produce smaller risk reductions. Thus, any physical activity is better than none, although higher volumes, even above the 2008 guideline recommendations, appear to further reduce CVD.

The Curvilinear Relationship Between Physical Activity and Cardiovascular Risk

A similar increase in physical activity yields different risk reductions across the activity spectrum. Physical inactivity is associated with the highest risk, whereas high aerobic exercise volumes are associated with the lowest risk (26).

Several studies have examined the minimum volume of aerobic physical activity required to produce health benefits. The least active, but still effective, behavior is standing. Standing >2 h/day is associated with a 10% reduction of all-cause mortality (hazard ratio [HR]: 0.90; 95% CI: 0.85 to 0.95) compared with standing <2 h/day (27). Increased standing time was associated with larger risk reductions, with the lowest mortality in individuals standing ≥8 h/day (HR: 0.76; 95% CI: 0.69 to 0.95), but standing time could have also included light physical activity, such as walking, in addition to only standing. The study population included 221,240 Australians age ≥45 years and the results were independent of health status and were not altered by sex, age, body mass index, other physical activity, and sitting time (27). Similar reductions in all-cause mortality with standing were observed prospectively in 16,586 Canadians (28), but this study also showed that standing 25% and 75% of the time was associated with 18% and 32% reductions in CVD mortality, respectively (HR: 0.82; 95% CI: 0.68 to 0.99 and HR: 0.68; 95% CI: 0.50 to 0.92) (28). This dose–response relationship between standing and CVD mortality informs on the lower end of the CVD benefit relationship and supports the concept that even small amounts of physical activity provide CVD benefit.

An additional benefit of the increase in time standing and performing light physical activity is the simultaneous reduction of even less taxing activities such as sitting. Prolonged sitting increases the risk for all-cause mortality in a dose-dependent fashion (29). Importantly, the detrimental effects of sitting appear to be independent from the benefits of physical activity (30). Recent studies demonstrate that breaking up sitting time improves cardiovascular health (31) and glucose homeostasis (32), and replacement of sitting time effectively reduces all-cause mortality (33). It is therefore recommended that future primary intervention programs target both sedentary behavior as well as habitual physical activity to maximize the reduction in cardiovascular risk.

The volume of aerobic exercise to improve CVD outcomes maximally is difficult to determine. The metabolic equivalent of task (MET) score uses the intensity of exercise (a multiple of the resting metabolic rate) from the Compendium for Physical Activities (37) multiplied by an assessment of the frequency (sessions/week) and duration (h/week) to calculate the exercise volume in MET-h/week. We combined data from Taiwanese (35), American, and European population studies (36) to assess the dose–response relationship between physical activity and CVD mortality (Figure 2). Maximal risk reduction for cardiovascular mortality was found at a volume of 41 MET-h/week. This is 3.5× to 4× greater than the recommended volume and equals 547 min/week of moderate-intensity exercise at 4.5 METs or 289 min/week of vigorous-intensity exercise at 8.5 METs. Individuals performing exercise at this volume experienced a 45% lower risk for CVD mortality (HR: 0.55; 95% CI: 0.46 to 0.66) compared with inactive control subjects.

The Dose-Response Curve of Physical Activity and Cardiovascular Mortality

On the basis of data from the studies of Wen et al. (35)(blue squares) and Arem et al. (36)(orange circles). The average exercise volume (MET-h/week) was calculated for the ranges of physical activity that were provided in the study by Arem et al. (36). The maximal risk reduction for cardiovascular mortality was found at an exercise volume of 41 MET-h/week. CVD = cardiovascular disease; MET = metabolic equivalent of task score.

Only 3.5% of individuals included in the meta-analysis mentioned exceed the exercise volume that was associated with maximal health benefits (36). These individuals experienced reductions in CVD mortality comparable to the “maximal benefit” group (HR: 0.61; 95% CI: 0.55 to 0.67; and HR: 0.71; 95% CI: 0.56 to 0.91 for subjects performing 40 to 75 MET-h/week and >75 MET-h/week, respectively) (36), but this difference was not statistically significant in part because the small percentage of individuals exercising at this volume creates large confidence intervals. Performing exercise volumes at the upper end of the physical activity spectrum therefore appears to be safe because there is no evidence for adverse CVD outcomes among these individuals.

Does intensity matter?

Moderate-intensity activities are defined as requiring 3.0 to 5.9 METs of energy expenditure, whereas vigorous intensity requires ≥6.0 METs. High-intensity interval training produces larger improvements in cardiorespiratory fitness, expressed as VO2max, compared with moderate-intensity, continuous training (38). Higher fitness levels are associated with a reduction in CVD (39) and all-cause mortality (40) in a curvilinear fashion. The potential superior health benefits of vigorous-intensity exercise are supported by epidemiological data. Australians performing <30% of their total physical activity in vigorous exercise, as well as those performing >30% had reduced mortality rates compared with individuals performing only moderate-intensity exercise (HR: 0.91; 95% CI: 0.84 to 0.98 and HR: 0.87; 95% CI: 0.81 to 0.93, respectively) after adjusting for total volume of moderate- to vigorous-intensity activities (41). These observations are consistent with a systematic review of epidemiological studies and clinical trials demonstrating a larger reduction in CVD events and improvement in CVD risk factors for vigorous versus moderate intensity physical activity (42).

Interestingly, the dose-response curve between physical activity and mortality appears to be different for moderate versus vigorous-intensity exercise (Figure 3). Increasing levels of moderate intensity physical activity progressively reduces CVD mortality, whereas the response curve flattens for vigorous physical activity in an excess of 11 MET-h/week (34,35). Similar patterns exist for all-cause mortality, although the differences between moderate and vigorous intensity activity were less pronounced (34–36) (Figure 3). These findings indicate that increasing volumes of moderate-intensity exercise are associated with further improvements in CVD health, whereas for vigorous intensity, lower volumes are associated with maximal risk reduction.

The Dose-Response Curve of Moderate- and Vigorous-Intensity Physical Activity and Cardiovascular and All-Cause Mortality

The dose-response curve of moderate-intensity (solid lines) and vigorous-intensity (dashed lines) physical activity and cardiovascular (left) and all-cause mortality (right) based on data from the studies of Wen et al. (35)(blue squares), Lee et al. (34)(gray triangles), and Arem et al. (36)(orange circles). The average exercise volume (MET-h/week) was calculated for the ranges of physical activity that were provided in the study by Arem et al. (36). These figures demonstrate that vigorous intensity activities already reach a maximum risk reduction at lower exercise volumes, whereas larger volumes of moderate intensity activities are associated with a further reduction in cardiovascular/all-cause mortality. PA = physical activity; other abbreviations as in Figure 2.

This relationship may be due at least in part to the repeated observation that vigorous-intensity exercise acutely, albeit transiently, increases CVD events (43–45). A total of 122 sudden cardiac deaths (SCDs), 23 (18.9%) of which were exercise related, occurred in a study of 21,481 male physicians (45). The absolute risk for a vigorous exercise-related SCD was low at 1 per 1.42 million hours, but 16.9% higher (95% CI: 10.5% to 27.0%; p < 0.001) than that during low/no physical activity. Despite this acute increase in risk during vigorous activity, the relative risk (RR) for SCD decreased progressively with increasing habitual vigorous exercise from an RR of 74.1 for those exercising vigorously <1 session/week (95% CI: 22.0 to 249) versus an RR of 18.9 for those exercising vigorously 1 to 4 sessions/week (95% CI: 10.2 to 35.1) versus an RR of 10.9 for those exercising vigorously ≥5 sessions/week (95% CI: 4.5 to 26.2) (45). The pattern is similar for the association between vigorous exertion and acute myocardial infarction (MI) in the general population (44). Among 1,228 MI patients, the risk for a vigorous activity-induced MI was markedly lower for individuals regularly involved in vigorous activities (≥5 sessions/week; RR: 2.4) compared with sedentary individuals (no sessions/week, RR: 107) (44). Such results demonstrate that vigorous physical activity transiently increases the risk for acute cardiac events, but reduces the overall risk.

In summary, volumes of moderate- and vigorous-intensity exercise below the 2008 Physical Activity Guideline recommendations result in a significantly lower mortality risk in different populations around the globe. Increasing volumes of moderate-intensity exercise result in larger reductions of CVD mortality, whereas no further reduction in CVD mortality is observed for volumes of vigorous-intensity exercise beyond 11 MET-h/week. Finally, there is no evidence for an upper limit of exercise-induced health benefits. Every volume of moderate- and vigorous-intensity aerobic exercise results in a reduction of all-cause and CVD mortality compared with physical inactivity.

Exercise in Secondary Prevention

Current guideline recommendations

Exercise is a key component in the management of patients with most established CVD because it reduces recurrent CVD events. Guidelines from the American College of Cardiology and American Heart Association include specific recommendations for diverse populations of cardiac patients (Table 2) (46–50). The recommend exercise volume is generally similar to that for healthy adults: 30 to 60 min/day of moderate-intensity aerobic activities. Exercise can be performed as a part of a clinical rehabilitation program or at home and in the community. Patients are advised to include resistance exercise training to maintain strength and muscle mass. A meta-analysis of 504 studies suggests that the combination of aerobic and resistance exercise produces greater reductions in body fat and improvements in muscle strength compared with aerobic exercise alone (51). Adding strength training to aerobic programs tends to produce larger increases in cardiopulmonary fitness and improvements in quality of life (QOL) in patients with CVD (51). Increased QOL may occur because the increases in exercise capacity and strength increase self-confidence and independence after a CVD event.

HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) examined the effect of exercise training in 2,331 patients with systolic heart failure and ejection fractions <35%. Subjects participated in 12 weeks of supervised thrice-weekly exercise training followed by an at-home training program. The investigators sought to enhance adherence to the home exercise by providing treadmills or stationary cycles to participants. Despite such efforts, adherence to the exercise training program was low and the average increase in maximal oxygen uptake was only 0.7 ml/kg/min (interquartile range [IQR]: –1.0 to 2.5 ml/kg/min), a value lower than most prior, smaller studies of exercise training in this population. Heart failure patients receiving exercise training had a reduced incidence of cardiovascular mortality and heart failure hospitalization compared to the nonexercise training usual care group (HR: 0.87; 95% CI: 0.75 to 1.00) (56). After correction for highly prognostic baseline factors and heart failure etiology, these findings became statistically significant (HR: 0.85; 95% CI: 0.74 to 0.99). Patients receiving exercise training also reported an earlier and larger improvement in self-reported health status, which persisted over time (57).

The volume and intensity of aerobic exercise training for secondary prevention

Most cardiac rehabilitation studies and programs used a relatively standard exercise protocol. Subjects generally exercised 3× weekly for 30 to 40 min/session at heart rates equal to 60% to 85% of their maximal value or age-estimated maximal value. The risk of cardiac arrest during vigorous exercise in individuals with CVD was initially estimated at 6× to 164× greater than their risk at rest (58). The risk of a cardiac event during contemporary cardiac rehabilitation is low: estimated at only 1 cardiac arrest per 116,906 patient-hours of participation and 1 fatality per 752,365 patient-hours (59). These event rates apply to supervised cardiac rehabilitation where trained personnel can monitor symptoms and administer resuscitation if needed. Comparing the cardiac arrest and mortality rates suggests that the fatality rate would be 6-fold higher without successful resuscitation performed by the rehabilitation staff.

There are few studies examining the effect of exercise volume on CVD outcomes in cardiac patients, because most studies used standard and similar exercise training protocols. Data from the HF-ACTION trial suggest a curvilinear response between the volume of exercise and the subsequent risk for cardiovascular events during 28 months of follow-up (60). Heart failure patients performing exercise ≥5 MET-h/week had a higher event-free survival compared with those performing lower volumes of exercise (i.e., <1, 1 to 3, or 3 to 5 MET-h/week). However, after correction for peak VO2 values, a J-shaped curve appeared, with the largest risk reductions in patients exercising 3 to 7 MET-h/week and less benefit for patients exercising ≥7 MET-h/week (60).

Several studies in CVD subjects exercising in unsupervised settings reinforce the hypothesis that high volumes of exercise may be deleterious in this patient group. The National Runners’ and Walkers’ Health studies of Williams et al. (10) recorded the baseline exercise habits and health outcomes of 2,377 subjects who were self-identified as heart attack survivors at baseline. A total of 526 died over an average follow-up of 10.4 years; 71.5% died due to CVD. CVD mortality decreased progressively with increasing amounts of exercise to a maximum mortality reduction of 63% in those running or walking at a volume of 38 to 50 MET-h/week compared with the least active group (<8 MET-h/week). In the most active exercisers, however, those running >7.1 km a day or walking briskly >10.7 km a day, the reduction in CVD mortality was only 12%, and was not different from the least active group (Central Illustration).

These data from Williams et al. (10) show an attenuation of mortality risk reductions in patients with the highest levels of exercise. Studies by both Wannamethee et al. (61) and Mons et al. (9) also show an apparent reduction in the benefit of exercise in the most active subjects. Among 772 British patients with coronary heart disease (61), lightly and moderately active patients had a significantly lower all-cause and CVD-related mortality risk compared with inactive patients, whereas moderately to vigorously active patients did not (Central Illustration). Similarly, Mons et al. (9) found that among 1,038 German coronary heart disease patients, patients exercising 2 to 4 sessions/week demonstrated the lowest all-cause (7.6 per 1,000 person-years) and cardiovascular mortality (4.5 per 1,000 person-years), whereas higher or lower exercise frequencies were associated with higher mortality rates (Central Illustration). In contrast, the examination by Moholdt et al. (62) of 3,504 Norwegian patients with coronary heart disease observed no attenuated mortality risk reduction in the most active group (Central Illustration). These current studies are limited by their observational nature, their use of self-reported activity patterns, and a potential selection bias of participating subjects. The possibility that high levels of exercise attenuate the reduction in CVD events warrants additional examination because of the widespread perception that more of a good thing is better. Hence, the extrapolation of these observations is limited and may only be of concern in a minority of patients.

Despite these concerns about the volume and intensity of exercise in CVD patients, several studies have explored strategies to optimize the effects of cardiac rehabilitation using high-intensity interval training (HIIT), modeled after athletic training programs. HIIT was introduced into cardiac rehabilitation in 2007 and typically consists of a 10-min warm-up at 60% to 70% of peak heart rate, followed by 4 4-min intervals at 90% to 95% of peak heart rate separated by 3-min active pauses at 50% to 70% of peak heart rate (63). The exercise session is ended by a 3-min cool down at 50% to 70% of peak heart rate (Figure 4).

The greater increase in cardiorespiratory fitness with more intense exercise training in CVD patients does not necessarily mean that the more intense training regimens will increase survival. There are also potential risks to more intense exercise in CVD patients especially if performed in the absence of trained medical personnel. A comparison of adverse CVD events between MICT and HIIT in 4,846 cardiac patients revealed event rates of 1 per 129,456 and 1 per 23,182 patient-hours, respectively (66). These data suggest a higher risk for adverse CVD outcomes with HIIT, but there were only 1 fatal cardiac arrest and 2 nonfatal cardiac arrests with MICT and HIIT, respectively, so there were too few events and insufficient power to compare risk.

Taken together, referral to an exercise rehabilitation program is recommended for cardiac patients, because participants benefit from a reduced risk for future cardiovascular events and mortality. Supervised HIIT protocols yield larger health improvements than MICT protocols. The risk for cardiac arrest and SCD during exercise is low but present. High-intensity activities and high weekly exercise volumes may attenuate the health benefits in cardiac patients, with risk rates returning to the level of inactive peers. Moderate-intensity exercise at volumes comparable to guidelines (46–50) should therefore be recommended for cardiac patients by their clinicians to achieve maximal cardiovascular benefits.

The Controversy of Excessive Exercise

The amount of habitual exercise training required to be a successful endurance athlete is markedly higher than that required for cardiovascular health. Multiple studies have reported unexpected, potentially adverse cardiovascular outcomes in athletes. For example, some athletes demonstrate exercise-induced elevations in cardiac troponin levels (67), evidence of myocardial fibrosis (68), post-exercise cardiac dysfunction (69), an increased incidence of arrhythmias (70), accelerated coronary artery calcifications (71), and an increased risk for cardiovascular morbidity and mortality at high amounts of exercise compared with light to moderate amounts of exercise (7,8). These observations among marathon runners, triathletes, cross-country skiers, and cyclists raise the question of whether such athletes may experience potentially detrimental cardiac side effects from their exercise habits (72).

Exercise-induced, acute elevations in cardiac troponin T and I are observed in athletes participating in running races (15, 21, or 42 km) (73), triathlons (74), endurance cycling (75), and ultra-endurance races (76), but also in individuals from the general population performing prolonged walking exercise (77). Post-exercise troponin concentrations are related to the covered distance (73) and exercise intensity (78), and exceed the upper reference limit for an acute MI in >50% of the athletic population (67). Although these findings suggest cardiac damage due to exercise performance, the kinetics of troponin release are different between patients and athletes. Athletes demonstrate modestly elevated peak troponin levels that normalize within 72 h post-exercise in absence of any signs or symptoms of ischemia (79). In contrast, peak troponin concentrations can increase up to 50× the upper limit of normal and remain elevated for 4 to 10 days in acute MI patients in conjunction with acute electrocardiogram changes and imaging evidence of ischemia (80). It is therefore hypothesized that troponin elevations in athletes represent a physiological rather than a pathological phenomenon (81), potentially caused by troponin leaks from the cytosol of cardiomyocytes due to an exercise-induced increase in membrane permeability.

Small cardiac foci of late gadolinium enhancement have been found during cardiac magnetic resonance imaging in some (68,82,83), but not all (84,85) studies of endurance athletes. These observations provide evidence of myocardial fibrosis, possibly increasing the risk of cardiac arrhythmia and mortality (86,87). The presence of myocardial fibrosis was observed in 12% to 50% of the athletes and was associated with longer endurance exercise participation and higher years of training and number of completed marathons (68,82,83). Fibrosis was frequently found where the right ventricle inserts into the septum, a location that is rarely observed in ischemic cardiac patients. Interestingly, comparable patterns are observed in hypertrophic cardiomyopathy patients (88). Similarly, faint late gadolinium enhancement has been observed at the superior and inferior insertion points of the right and left ventricles of patients whose right ventricle was forced to produce systemic pressures after atrial redirection surgery for transposition of the great vessels (89). This suggests a nonischemic etiology for the fibrosis found in athletes and that it is possibly due to the increase in mechanical stress on the right ventricle during exercise (90). Nevertheless, athletes with late gadolinium enhancement demonstrated a worse event-free survival compared with those without imaging abnormalities (75% vs. 99%; p < 0.001) in 1 study (82).

Post-exercise decreases in left and right ventricular function are observed in some endurance athletes, with a larger decrement in the right versus left ventricle (76,91). The magnitude of the reduction in cardiac function is associated with longer exercise duration (68) and lower training status (92). This cardiac dysfunction is mild and typically recovers within 48 h after exercise cessation (93). Exercise-induced right ventricular dysfunction appears to be more pronounced in athletes with ventricular arrhythmias compared with healthy athletes (94). Whether athletes with a transient decline in cardiac function are at risk for future arrhythmias is currently unknown.

The association between physical activity patterns and incident atrial fibrillation is complicated. More leisure-time activity, greater walking distance, faster walking pace, and higher cardiorespiratory fitness were associated with a graded risk reduction for atrial fibrillation in the Cardiovascular Health Study (N = 5,446) and Henry Ford Exercise Testing (FIT) Project (N = 64,561) (95,96). In contrast, a meta-analysis (N = 1,550) reported a 5-fold increase in the relative risk for atrial fibrillation in athletes (OR: 5.3; 95% CI: 3.6 to 7.9) compared with the general population (97). Also, a large Swedish study (N = 52,755) confirmed these findings and observed a higher incidence of atrial fibrillation in participants completing ≥5 versus 1 Vasaloppet cross-country ski-races (HR: 1.29; 95% CI: 1.04 to 1.61) and in those with faster finishing times (100% to 160% vs. >240% of winning time; HR: 1.20; 95% CI: 0.93 to 1.55). A potential explanation for these apparently contradictory findings is that the relationship between physical activity may be U-shaped, with moderate amounts of exercise decreasing but large volumes of exercise increasing atrial fibrillation risk (96,98).

The physically active lifestyle of athletes does not prevent the development of central and peripheral atherosclerosis (99). In fact, greater coronary artery calcification (CAC) scores have been found in German marathon runners (median 36; IQR: 0 to 217) compared with control subjects (median 12; IQR: 0 to 78) matched for age and Framingham risk score (71), but this difference disappeared when the authors corrected for age only (median 38; IQR: 3 to 187). Alternatively, the elevated CAC scores may be the result of plaque stabilization, as a higher CAC density is protective for future cardiovascular outcomes (100). This hypothesis aligns with epidemiological observations of reduced cardiovascular morbidity and mortality in athletes compared with sedentary control subjects (101).

Two recent epidemiological studies reported a U-shaped relationship between aerobic exercise volumes and cardiovascular morbidity (8) and mortality (7) in the general population. A British study (N = 1,119,239) showed a lower incidence of cerebrovascular disease (RR: 0.81; 95% CI: 0.78 to 0.84) and venous thromboembolism (RR: 0.83; 95% CI: 0.79 to 0.87) in women performing 2 to 3 sessions/week of strenuous activities compared with inactive control subjects, but these health benefits disappeared in women performing daily strenuous activities (RR: 0.96; 95% CI: 0.89 to 1.04; and RR: 1.08; 95% CI: 0.99 to 1.17, respectively) (8). In contrast, daily activities regardless of the exercise intensity did reduce the incidence of cerebrovascular disease (RR: 0.88; 95% CI: 0.86 to 0.91) and venous thromboembolism (RR: 0.96; 95% CI: 0.93 to 1.00) compared with inactive control subjects. Also, any volume of (strenuous) exercise reduced the risk for incident coronary heart disease, even in women performing daily strenuous exercise (RR: 0.89; 95% CI: 0.84 to 0.93) (8). An important caveat of this study was the higher smoking prevalence among daily strenuous exercisers (25.6%) compared with all other exercise groups (13.7% to 15.5%). This may partially explain the absence of exercise-induced health benefits in the most active individuals. A Danish study including joggers (n = 1,098) and nonjoggers (n = 3,950) reported similar findings for all-cause mortality (7). Arbitrarily classified “light” joggers (HR: 0.22; 95% CI: 0.10 to 0.47) had a lower mortality risk compared with nonjoggers, whereas mortality rates in “moderate” (HR: 0.66; 95% CI: 0.32 to 1.38) and “strenuous” joggers (HR: 1.97; 95% CI: 0.48 to 8.14) were comparable to nonjoggers (7). For any other classification of physical activity (quantity, frequency, or pace), however, the most active group always demonstrated a lower mortality compared with nonjoggers. Other important study limitations include the low number of subjects in the strenuous jogger group and the fact that inclusion in the nonjoggers group allowed participants to walk or bike up to 2 h/week (102). Given the methodological limitations of these 2 studies, it is premature to conclude that high exercise volumes, compared with light to moderate volumes, could increase CVD risk.

The exercise-induced changes in cardiac structure and function are often related to the volume (late-gadolinium enhancement, cardiac dysfunction, and CAC) and intensity (troponin release and atrial fibrillation) of activities performed by athletes. For most observations, the long-term clinical implications are currently unknown, but it is unlikely that these are similar to risk classifications in CVD patient populations. For example, recreational marathon training has been shown to have a positive effect on several determinants of cardiovascular risk (103). Also, lifelong patterns of “committed” exercise (4 to 5 sessions/week) and “competitive” Masters-level athletes prevents most of the age-related left ventricular stiffening changes implicated in the pathophysiology of many cardiovascular disorders (104). Furthermore, leisure-time runners have lower all-cause (HR: 0.70; 95% CI: 0.64 to 0.77) and cardiovascular mortality rates (HR: 0.55; 95% CI: 0.46 to 0.65) compared with nonrunners (34). These observations are not limited to amateur athletes, but include elite athletes, who were engaged in high volumes of vigorous exercise for many years, yet demonstrated a 3- to 6-year increase in life expectancy compared with control subjects from general (105–107) and military (108) populations. Mortality risk reductions were larger for older athletes and those who participated in multiple races (101). These findings suggest that athletes performing exercise volumes at the upper end of the physical activity spectrum do not demonstrate an increased risk for adverse cardiovascular outcomes on a population level.

Even though exercise and exercise training appears to benefit the majority of people, there may be individuals with genetic predisposition for cardiac disease in whom exercise training is not beneficial. Physically active individuals with genetic defects in the desmosomal proteins associated with right ventricular cardiomyopathy presented earlier in life and had signs of more aggressive disease than less physically active individuals with similar genetic mutations (109). Whether similar patterns exist for other genetic mutations is worthy of investigation.

Conclusions

This review demonstrates that even small amounts of physical activity, including activities such as standing, are associated with lower CVD risk. Exercise volumes of 150 min/week of moderate-intensity or 75 min/week of vigorous-intensity aerobic exercise, such as recommended in the 2008 Physical Activity Guidelines Advisory Committee Report, further reduce CVD mortality. The possibility that too much exercise training could produce deleterious cardiac effects including myocardial fibrosis, coronary calcification, and atrial fibrillation is interesting and worthy of scientific investigation; however, overall the results, even for very active, life-long endurance athletes, is that the benefits of exercise training outweigh the risks. There may also be small subsets of the population with genetic predispositions to cardiac disease for whom vigorous exercise is not beneficial and may even be deleterious, although this represents a very small subset of patients. Moreover, the issue for most developed countries and the majority of their citizens is not concern about too much exercise, but rather the absence of any exercise among most of the population and among patients with CVD. For example, only 62% of 58,269 post-infarction patients were referred to cardiac rehabilitation at hospital discharge (110), whereas only 23% attended ≥1 cardiac rehabilitation session and only 5.4% completed ≥36 sessions. This may reflect, in part, a lack of clinician enthusiasm for such programs despite the evidence that cardiac rehabilitation saves lives. The available evidence should prompt clinicians to strongly recommend low and moderate exercise training for the majority of our patients. Equally important are initiatives to promote population health at large through physical activity across the life span, as it modulates behavior from childhood into adult life.

Footnotes

The views expressed in this paper by the American College of Cardiology's (ACC's) Sports and Exercise Cardiology Leadership Council do not necessarily reflect the views of the Journal of the American College of Cardiology or the ACC.

Dr. Eijsvogels is supported by a European Commission Horizon 2020 grant (Marie Sklodowska-Curie Fellowship 655502). Dr. Thompson has received research support from the National Institutes of Health, Genomas, Aventis, Roche, Sanofi, Regeneron, Esperion, Amarin and Pfizer; has served as a consultant for Amgen, AstraZeneca, Regeneron, Merck, Genomas, Abbott, Pfizer, Esperion, and Sanofi; has received speaker honoraria from Merck, AstraZeneca, Regeneron, Sanofi, and Amgen; owns stock in Abbvie, Abbott Laboratories, CVS, General Electric, Johnson & Johnson, Medtronic, and JA Wiley; and has provided expert legal testimony on exercise-related cardiac events and statin myopathy. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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